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Authors Shen Y, Pi Z, Yan F, Yeh CK, Zeng X, Diao X, Hu Y, Chen S, Chen X, Zheng H
Received 19 March 2017
Accepted for publication 4 July 2017
Published 9 August 2017 Volume 2017:12 Pages 5613—5629
DOI https://doi.org/10.2147/IJN.S136401
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Akshita Wason
Peer reviewer comments 3
Editor who approved publication: Dr Lei Yang
Abstract: Paclitaxel liposomes (PTX-LIPO) are a clinically promising
antineoplastic drug formulation for the treatment of various extracranial
cancers, excluding glioblastoma. A main reason for this is the presence of the
blood–brain barrier (BBB) or blood–tumor barrier (BTB), preventing liposomal
drugs from crossing at a therapeutically meaningful level. Focused ultrasound
(FUS) in conjunction with microbubbles (MBs) has been suggested in many studies
to be an effective approach to increase the BBB or BTB permeability. In this
study, we investigated the feasibility of enhancing the delivery of PTX-LIPO in
intracranial glioblastoma-bearing nude mice using pulsed low-intensity FUS
exposure in the presence of MBs. Our results showed that the delivery
efficiency of PTX-LIPO could be effectively improved in terms of the
penetration of both the BBB in vitro and BTB in vivo by pulsed FUS sonication
with a 10 ms pulse length and 1 Hz pulse repetition frequency at 0.64 MPa
peak-rarefactional pressure in the presence of MBs. Quantitative analysis
showed that a 2-fold higher drug concentration had accumulated in the
glioblastoma 3 h after FUS treatment, with 7.20±1.18 µg PTX per g glioma
tissue. Longitudinal magnetic resonance imaging analysis illustrated that the
intracranial glioblastoma progression in nude mice treated with PTX-LIPO
delivered via FUS with MBs was suppressed consistently for 4 weeks compared to
the untreated group. The medium survival time of these tumor-bearing nude mice
was significantly prolonged by 20.8%, compared to the untreated nude mice.
Immunohistochemical analysis further confirmed the antiproliferation effect and
cell apoptosis induction. Our study demonstrated that noninvasive low-intensity
FUS with MBs can be used as an effective approach to deliver PTX-LIPO in order
to improve their chemotherapy efficacy toward glioblastoma.
Keywords: paclitaxel
liposomes, focused ultrasound, microbubbles, blood-brain barrier